[D-Ala2, D-Leu5] Enkephalin Improves Liver Preservation During Normothermic Ex Vivo Perfusion

Beal, Eliza W.; Kim, Jung‐Lye; Reader, Brenda F.; Akateh, Clifford; Maynard, Katelyn; Washburn, W. Kenneth; Zweíer, Jay L.; Whitson, Bryan A.; Black, Sylvester M.

doi:10.1016/j.jss.2019.04.010

Cited by 28 publications

(22 citation statements)

References 31 publications

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“…In a study of hepatic IRI in normal rats, DADLE could protect hepatocytes by reducing the cellular metabolism (25). Besides, it was observed that DADLE could prevent cellular mitochondrial dysfunction through opioid receptor signaling involvement in vitro (16). In this paper, the beneficial effects of DOR activation and potential mechanism were further studied and identified in the hepatic IRI model in cirrhotic rats: (1) The optimal protective dose of DADLE in hepatic IRI (5 mg•kg −1 ), the administration route, intravenous injection, and the time point, 10 min prior hepatic ischemia, followed by a 6-h reperfusion, were identified.…”

Section: Discussionmentioning

confidence: 99%

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[D-Ala2, D-Leu5] Enkephalin Attenuates Hepatic Ischemia–Reperfusion Injury in Cirrhotic Rats

et al. 2022

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Background and AimsHepatic ischemia–reperfusion injury (IRI) is a common phenomenon that occurs after liver transplantation and liver tumor surgery. It can cause liver dysfunction and recovery failure after liver surgery, even leading to acute liver failure. Our aim is to investigate the protective effect and related potential mechanism of [D-Ala2, D-Leu5] enkephalin (DADLE) treatment on hepatic IRI in cirrhotic livers of rats.MethodsThe models of liver cirrhosis and hepatic IRI were established with male Sprague–Dawley rats. DADLE at a dose series of 0.5, 1, or 5 mg·kg−1 was injected intravenously to rats 10 min prior hepatic ischemia, followed by a 6- h reperfusion. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histological changes, and liver cell apoptosis were used to assess liver IRI. The optimal dose of DADLE was assessed by using the Suzuki score and ALT and AST levels. We repeated the hepatic IRI procedure on the optimal dose of the DADLE group and the delta opioid receptor (DOR) antagonist natrindole hydrochloride (NTD) injection group. Serum ALT and AST levels, histological staining, hepatic apoptosis, and serum levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 β (IL-1β) were measured. The expression of protein kinase B (Akt) and its downstream proteins were evaluated by using quantitative real-time polymerase chain action (qRT-PCR) and Western blotting.ResultsCompared with the control group, DADLE treatment at a dose of 5 mg·kg−1 reduced the Suzuki score (mean: 5.8, range: 5.0–6.6 vs. mean: 8.0, range: 7.0–8.9), the ALT level (134.3 ± 44.7 vs. 247.8 ± 104.6), and the AST (297.1 ± 112.7 vs. 660.8 ± 104.3) level. DOR antagonist NTD aggravated hepatic IRI. Compared with the control group, DADLE treatment decreased the number of apoptosis cells and microphages and neutrophils, increased the expression of Akt and its mRNA to much higher levels, and upregulated the mRNA and protein expression of Bcl-2 and Bcl-2-associated death promoter (BAD).ConclusionDADLE treatment at a dose of 5 mg·kg−1 injected intravenously 10 min prior hepatic ischemia could contain rats’ hepatic IRI by activating DOR in cirrhotic livers. The effects of DADLE could be offset by NTD. The potential molecular mechanism seems to be involved in the phosphatidylinositol-3-kinase (PI3K)/Akt pathway.

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Section: Discussionmentioning

confidence: 99%

“…Recently, other researchers found that DOR triggered a protective effect by reducing cellular metabolism, which resulted in ameliorating hepatic IRI (30). It was also found that DOR activation by DADLE could preserve perfused liver lobes via the antiapoptosis pathway (16). Apoptosis is a major element for cellular death after hepatic IRI.…”

Section: Discussionmentioning

confidence: 99%

[D-Ala2, D-Leu5] Enkephalin Attenuates Hepatic Ischemia–Reperfusion Injury in Cirrhotic Rats

et al. 2022

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“…This represents an exciting new frontier in liver transplants. The field of machine perfusion therapeutics in liver transplant is focused on defatting cocktails, vasodilators, anti-inflammatory agents, mesenchymal stem cell therapy, and gene therapy to optimise the graft during ex vivo NMP [73][74][75][76][77][78][79][80][81][82][83][84][85] .…”

Section: Therapeutic Strategies During Ex Vivo Machine Perfusionmentioning

confidence: 99%

A Review of Machine Perfusion Strategies in Liver Transplantation

Banker¹,

Bhatt²,

Rao³

et al. 2023

Journal of Clinical and Experimental Hepatology

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“…Enkephalin, an opioid agonist of delta receptors, has been administered during rat liver NMP obtaining a reduction of oxidative stress, as demonstrated by lower AST, MDA and glutathione levels, increased ATP synthesis and preserved tissue integrity 122 . The Groningen group has used metformin to precondition rat livers before NMP, resulting in improved hepatobiliary function and lower post-transplant transaminases 123 .…”

Section: Further Applications Of Nmp In Drug Deliverymentioning

confidence: 99%

Some Like It Hot. Utility and Mechanisms of Ex-Situ Normothermic Machine Perfusion of the Liver

Patrono

Stefano

Rigo

et al. 2023

EJT

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The need for donor pool expansion in liver transplantation has increased utilization of grafts from so-called extended-criteria donors. Machine perfusion technology can improve preservation of these grafts, and its use has been associated with improved short-and long-term outcomes. During normothermic machine perfusion the graft is preserved at 37°C, and continuously supplied with oxygen and nutrients. The main advantages of this preservation technique are the reduction of ischemia-reperfusion injury, the prolongation of preservation time, and the possibility to assess graft viability or delivering therapies ex-vivo. However, it is still considered as a complex technique, which has elicited some reticence about its utilization among transplant professionals. The aim of this narrative review is to give a synthetic but comprehensive update on normothermic machine perfusion in liver transplantation, discussing its fundamental principles and clinical implications. Technical and procedural aspects, along with physiological bases, will be discussed. Results of clinical trials will be summarized, including those highlighting the role of this technology in the delicate process of assessing liver viability and its impact on transplant logistics. Finally, latest findings in the field of basic and translational research on organ reconditioning will be reported.

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[D-Ala2, D-Leu5] Enkephalin Improves Liver Preservation During Normothermic Ex Vivo Perfusion

Cited by 28 publications

References 31 publications

[D-Ala2, D-Leu5] Enkephalin Attenuates Hepatic Ischemia–Reperfusion Injury in Cirrhotic Rats

[D-Ala2, D-Leu5] Enkephalin Attenuates Hepatic Ischemia–Reperfusion Injury in Cirrhotic Rats

A Review of Machine Perfusion Strategies in Liver Transplantation

Some Like It Hot. Utility and Mechanisms of Ex-Situ Normothermic Machine Perfusion of the Liver

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